Our aim is to develop a simple method for the delivery of anthrax vaccines by topical application of adenovirus-based expression vectors using a skin patch in a noninvasive mode. The hypothesis is that the expression of Bacillus anthracis protective antigen (PA) in the outer layer of skin can induce a systemic immune response against PA, and thereby protect the vaccinee by preventing the lethal factor (LF) and edema factor (EF) from gaining their access into target cells. We have demonstrated that an immune response against a number of antigens could be elicited in animal models by noninvasive vaccination onto the skin (NIVS). These studies will further develop skin-targeted noninvasive vaccines, and specifically determine whether this novel approach for the delivery of vaccines can mobilize the immune repertoire toward a beneficial immune protection against anthrax. In this project, the potential for skin-targeted noninvasive vaccines to elicit a protective immune response against anthrax will be investigated. A new generation of adenoviral vectors as novel vaccine carriers will be developed. Efficacy of NIVS will be compared to those induced by other means. The safety for NIVS will be studied by determining the fate of antigen DNA. The overall goal of these experiments is to determine whether anthrax vaccines can be effectively and safely delivered by a skin patch that requires a lower level of skill in a needle-free manner. PROPOSED COMMERCIAL APPLICATION: Noninvasive vaccination onto the skin may boost vaccine coverages against anthrox during an emergency becuse the procedure is simple, effective, painless, and potentially safe. The development of an anthrax vaccine patch may also make vaccination programs less dependent upon medical resources.